The leading cause of death in men and women in the U.S. is cardiovascular disease. Its early detection is the key in reducing the associated death toll. The general objective of this project is to develop a highly reliable and low-cost imaging technique for the mapping of ischemia and infarction. The underlying hypothesis of this grant is that ultrasound elastography can, in the myocardium, detect and quantify the extent of ischemia and infarction, at and beyond its onset due to the associated significantly altered stiffness of the muscle. Further benefiting from the real-time capability and portability of this technology, this information can ultimately be delivered in an emergency room setting to aid the early diagnosis and treatment of people suffering from myocardial infarcts. Before these benefits can be realized, however, the elastographic technique must be validated and angle-independent regional deformation estimates of the myocardium throughout a cardiac cycle obtained through the use of a theoretical, biomechanical analysis, experimental phantoms and appropriate animal models. The proposed methodology will also be compared to the current gold standard for mapping of myocardial deformation, MRI tagging techniques. The specific aims of this project are thus to: 1) refine a reliable theoretical model to determine the elastographic imaging quality in both normal and ischemic simulated cases; 2) generate myocardial elastograms on tissue- mimicking phantoms with varying stiffness (simulating onset of infarct) at distinct motion configurations; 3) investigate the potential of Myocardial Elastography as an early detection imaging tool at varying degrees ischemia in a controlled setting of canine hearts in vivo; 4) validate Myocardial Elastography estimates against MR cardiac tagging findings on a previously established in vivo human database. Should the results of this study indicate high reliability of the elastographic findings for detection of early ischemic onset, this novel imaging technique could be readily applied in an emergency room setting as part of a standard clinical protocol for early detection, and thus prevention, of myocardial infarction. The eventual goal of this technology is thus to become a specific method in standard clinical practice for real-time imaging of the position and severity of contraction defects in cardiac infarcts or angina, improving care and outcomes at little more cost or risk than that of a clinical ultrasound. [unreadable] [unreadable] [unreadable]